Is vasoactive intestinal polypeptide the principal transmitter involved in human penile erection?

Previous work from this laboratory reported on the effects of several autacoids and other agents on strips of human corpus cavernosum (cc) muscle. These investigations indicated the presence in the cc muscle of a) atropine-sensitive cholinoceptors, b) alpha- and beta-adrenoceptors and c) a non-adrenergic non-cholinergic mechanism. Several recent publications have presented evidence in support of the possibility that vasoactive intestinal polypeptide (VIP) is an important, or the chief, transmitter in human penile erection. This paper describes the actions of VIP and other compounds on the cc muscle and the effect of intracavernous injection of VIP in volunteers. Among the agents tested, VIP was the most potent relaxant of the cc muscle. This effect, which was seen at a dose as low as 0.03 nM, was suppressed by VIP antiserum. The response of the isolated penile vasculature to VIP was similar. VIP antiserum had no effect on the relaxation of the cc muscle produced by field stimulation. In five of the seven subjects given intracavernous VIP (1.0 micrograms.) some degree of penile enlargement was evident, but none had an erection. It is suggested that local release of VIP, withdrawal of the alpha-adrenoceptor mediated tonic supply to the penis and the activation of the latter's beta-adrenoceptors are all probably involved in penile erection in man.     

Digital tourniquets: a pressure study with clinical relevance

This study measured the pressures under the three most commonly used digital tourniquets--the Penrose drain, the rolled rubber glove, and the rubber band. A miniature pressure transducer and a digital strain indicator were used to measure pressures generated by the various tourniquets. The rolled rubber glove technique was highly consistent, irrespective of the clinical experience of the subject, and uniformly generated pressures of less than 500 mm Hg. Pressures generated by Penrose drains and rubber bands were highly variable and were significantly greater than 500 mm Hg. The so-called calibrated Penrose drain generated the highest pressures in the study. The relationship between tourniquet pressures and neurovascular injury in the human digit is not clearly defined.     

Pharmacological analysis of the interaction between Bay K 8644 and 5-HT in rabbit aorta

Bay K 8644 potentiated and augmented 5-hydroxytryptamine (5-HT)-induced contractions in the rabbit, isolated aorta preparation, as manifested in leftward shift and increase in the asymptote of 5-HT E/[A] (effect vs concentration) curves. The operational model of agonism (Black & Leff, 1983) was used to analyse this interaction and the concomitant effects of irreversible receptor alkylation by phenoxybenzamine. The competitive effects of spiperone in the presence and absence of Bay K 8644 were also examined. From these analyses it is concluded that Bay K 8644 elicits its potentiating effects by increasing the efficacy of 5-HT at the 5-HT2 receptor with no alteration in affinity. This is consistent with the known effect of Bay K 8644 of causing an increase in the functional concentration of plasmalemmal calcium channels coupled to the 5-HT2 receptors in this preparation. The positively co-operative shape of the 5-HT E/[A] curves obtained in the aorta and the quantitative nature of their potentiation by Bay K 8644 indicated that the coupling of 5-HT2 receptor occupancy to intracellular calcium concentration is linear and that the co-operativity resides in the subsequent relation between intracellular calcium and pharmacological effect. Bay K 8644 may serve as a probe for differentiating between the types of calcium channels that transduce 5-HT receptor-mediated effects in different systems. Such information would be useful in the classification of agonist interactions with 5-HT receptors.     

Bone turnover in postmenopausal women after withdrawal of estrogen/gestagen replacement therapy

Bone turnover before and after withdrawal of estrogen/gestagen treatment was studied in a randomized trial with 110 healthy female volunteers, who had passed a natural menopause 6 months to 3 years before the start of the study. Urinary excretion of intravenously injected 99m-technetium diphosphonate was measured as an index of bone turnover; plasma bone Gla protein and serum alkaline phosphatase were measured as indices of bone formation; and fasting urinary excretion of hydroxyproline and calcium were measured as estimates of bone resorption. During 2 years of hormone treatment, all variables decreased highly significantly (p less than 0.001) to a constant low level. Three months after withdrawal all variables increased highly significantly (p less than 0.001) towards, but not above, pretreatment and placebo levels. We conclude that withdrawal of estrogen/gestagen replacement therapy in postmenopausal women increases bone turnover, but not in excess of pretreatment values. This indicates that bone loss (after withdrawal) is similar to that seen in the placebo group and that a rebound phenomenon is unlikely.     

On verification of hyperthermia treatment planning for cervical carcinoma patients.

PURPOSE: The aim of this study was to verify hyperthermia treatment planning calculations by means of measurements performed during hyperthermia treatments. The calculated specific absorption rate (SAR(calc)) was compared with clinically measured SAR values, during 11 treatments in seven cervical carcinoma patients. METHODS: Hyperthermia treatments were performed using the 70 MHz AMC-4 waveguide system. Temperatures were measured using multisensor thermocouple probes. One invasive thermometry catheter in the cervical tumour and two non-invasive catheters in the vagina were used. For optimal tissue contact and fixation of the catheters, a gynaecological tampon was inserted, moisturized with distilled water (4 treatments), or saline (6 treatments) for better thermal contact. During one treatment no tampon was used. At the start of treatment the temperature rise (DeltaT(meas)) after a short power pulse was measured, which is proportional to SAR(meas). The SAR(calc) along the catheter tracks was extracted from the calculated SAR distribution and compared with the DeltaT(meas)-profiles. RESULTS: The correlation between DeltaT(meas) and SAR(calc) was on average R = 0.56 +/- 0.28, but appeared highly dependent on the wetness of the tampon (preferably with saline) and the tissue contact of the catheters. Correlations were strong (R approximately 0.85-0.93) when thermal contact was good, but much weaker (R approximately 0.14-0.48) for cases with poor thermal contact. CONCLUSION: Good correlations between measurements and calculations were found when tissue contact of the catheters was good. The main difficulties for accurate verification were of clinical nature, arising from improper use of the gynaecological tampon. Poor thermal contact between thermocouples and tissue caused measurement artefacts that were difficult to correlate with calculations.